Dougan Group | Microbial Pathogenesis

Dougan Group | Microbial Pathogenesis

Dougan Group

Sanger Institute, Genome Research Limited

Our Research and Approach

Background

Infectious diseases still pose a threat at a global and local level, particularly as disease agents can evolve so quickly. For example, bacteria such as Salmonella and Shigella cause intestinal infections that can have devastating consequences particularly in developing countries, but bacterial strains such as these can be resistant to almost all antibiotics.

New approaches are needed to treat bacterial infections, one of which is focusing on understanding the methods by which the body's natural systems fight off the tens of thousands of potentially pathogenic bacteria to which it is exposed in ordinary everyday life.

A complementary challenge is investigating how disease agents change to prevent human intervention. Understanding the molecular basis of infection could assist in attempts to develop vaccines and other therapies to protect against infections.

This information will be exploited towards developing methods of controlling infection, including vaccines and antibiotics, in the continuing fight against disease that is crucial for populations worldwide.

The team is also investigating the relationships between different members of the family of bacteria that cause typhoid, Salmonella Typhi, in order to explain their evolution, antibiotic resistance and transmission within the human population.

Finally the team is involved in a number of major high profile collaborations worldwide investigating methods for developing vaccines against typhoid, dysentery, malaria, and tuberculosis, all critically important diseases particularly in developing countries.

Research aims

The Microbial Pathogenesis team is dedicated to understanding the fundamental interactions that occur between the host i.e. the infected human or mouse - and the pathogen; and also to understanding the evolution of members of the families of the pathogen that causes typhoid and how this affects transmission of the disease in human populations. We use genetics as a core tool, studying both the host and the pathogen.

Our approach

We are running an integrated research programme that uses a variety of genetic approaches to study host-pathogen interactions. We are also undertaking a detailed molecular analysis of microbial populations through a faculty research programme, as well as providing significant support to Pathogen Genomics (formerly the PSU) and Mouse Genetics research groups.

People

Group Leader

Professor Gordon Dougan's research focuses on the genetic analysis of host/pathogen interactions during infection, particularly those involving enteric bacteria. He has worked extensively in both academia and industry, making important contributions in the field of vaccinology where he has worked to improve vaccine delivery to poorly resourced regions.

Oude Munnink, Bas

Phan, My

Smith, Sarah

Watson, Simon

Key Projects, Collaborations, Tools & Data

Faculty Programme Overview: We are focusing our research around the biology of intestinal bacterial infections, with a strong emphasis on invasive Salmonella disease. We work closely with other Faculty Groups in this and other Programmes of the Sanger Institute and have generated information on the genome sequences of a number of different Salmonella species or serovars including Bongori, Typhi, Typhimurium, Enteritidis, Gallinarum, Hadar, Infantis, Senftenberg and Paratyphi A that cause potentially lethal diseases such as typhoid and salmonella food poisoning. With Dr Trevor Lawley's Faculty Group, we have also determined the phylogenetic structure of C. difficile. We are using the information to investigate, at the genetic level, what makes different species of bacteria more potent (or virulent), in terms of their ability to cause disease, than others. To complement this research we are creating 'libraries' of pathogen strains that have single genes disabled in order to investigate their (the genes') functions and effects on virulence.We are also undertaking an analysis of microbial population structure in collaboration with Dr Mark Achtman at the Max Planck Institute for Infection Biology, Berlin, and Dr Stephen Baker at the Wellcome Unit in Ho Chi Minh City. We are concentrating efforts on Salmonella Typhi, which causes typhoid, and C. difficile, a common cause of infection in hospitals but have projects on other pathogens including Vibrio cholerae. We use DNA sequencing and gene-functionality based approaches, and exploit this information for biological experimentation. Another key study involves the analysis of the genome of S. typhimurium, responsible for invasive bacterial disease throughout Africa. This is run in collaboration with Dr Sam Kariuki in Nairobi and the Wellcome Unit in Blantyre, Malawi.Mouse genetic infection susceptibility project (Deputy Head, Dr Simon Clare): We run a mouse genetics project in which mice with an artificially disabled gene are challenged with certain pathogens. The aim is to identify mammalian genes that contribute to controlling susceptibility to infection. The main infectious agents used in this screen are currently S. typhimurium and Citrobacter rodentium, although other pathogens can be exploited to investigate genetic effects in detail.

Research Programmes and Faciltites

We are using genomics to get at important problems in infectious disease, with a strong desire to translate this into tools for disease control and elimination, but we are also at the forefront of basic research into microbial ecology, evolutionary genetics and the biology of parasitism.

The Infection Genomics Programme investigates the common underpinning mechanisms of evolution, infection and resistance to therapy in viruses, bacteria and parasites. The Programme also focuses on the genetics of host response to infection and the role of the microbiota in health and disease.

Partners and Funders

Internal Partners

Our group consistis of a mix of genomic epidemiologists, computational biologists and web software engineers within The Centre for Genomic Pathogen Surveillance (CGPS) a collaboration with imperial College London.

Within CGPS, broad aims are to provide data and tools for local, national and international utility focused on antimicrobial resistance and genomic surveillance. We are addressing the utility of large-scale structured pathogen surveys to provide contextual WGS datasets and population structure. Key aims are to enable the identification of high risk clones of public health importance, their risk assessment (eg resistance, virulence and transmissibility) and ultimately management.

We are collaborating with Gordon Dougan's team on high-throughout phenotyping of host and bacterial cells, as well as the development of new therapeutic strategies based on an understanding of antibiotic resistance.

The host-microbiota Interactions laboratory studies the mechanisms that underlie how micro-organisms in the gut, nasopharynx and uro-gential tract interact with their host during periods of health and disease. In particular the team seek to develop novel ways to treat diseases that are associated with unwanted imbalances in the micro-organism population.

We use various approaches including genetics, genomics and cell biology to study gene functions in normal development and disease such as cancer. We are particularly interested in stem cell self-renewal, differentiation, and lineage choice.

The Pathogen Informatics team develop and maintain software applications and systems to support the research activities of the pathogen group. We develop and maintain scalable and robust automated tools for sequence and annotation tracking and analysis and provide ad-hoc informatics support and training to the researchers in the pathogen group.